1. Area of the Art
The present invention relates to compositions and methods for eye and contact lens care. More particularly, the invention relates to ophthalmic compositions which contain cetylpyridinium chloride as a decontaminating agent for preservation of the solution and/or disinfecting contact lenses.
2. Description of the Prior Art
Contact lens wear induces adverse changes in ocular tissues and the tear film. These changes include cornea lactic acidosis and subsequent cornea swelling as a consequence of hypoxia induced by low oxygen gas transmission, changes in corneal epithelial tissue thickness, changes in corneal epithelial and endothelial cell morphology, epithelial surface cell exfoliation, hyperemia (red eye), adverse changes in corneal and conjunctival cell membrane integrity and destabilization of the tear film. Changes in cell membrane integrity can be measured clinically via measurements of lactate dehydrogenase enzyme release, fluorescein barrier permeability or other methods. Corneal epithelial cell membrane integrity is believed to be critical to maintain a tissue barrier function to prevent ocular infection.
Adverse changes in ocular tissues during contact lens wear also may arise due to exposure of ocular tissues to preservatives, disinfecting agents, cleaning agents and other components in the contact lens care solutions. This can occur through tissue contact with solutions which may directly contact ocular tissues during application or tissue contact with solutions which may absorb to the contact lens during treatment of the contact lens by the solution, and subsequently desorb from the contact lens during wear into the eye.
Contact lens solutions have become complex formulations of multiple components which provide several functions. Attempts have been made to ameliorate the adverse effects of contact lenses and contact lens care solutions on ocular tissues, with mixed results. The best examples of success in changing contact lens care solutions to ameliorate their adverse effects on ocular tissues is represented by the creation of polymeric contact lens disinfecting agents, antimicrobial systems which do not bind to contact lens surfaces and the inclusion of water-soluble polymers and electrolytes such as potassium chloride, magnesium and calcium chloride into contact lens multi-purpose and rewetting solutions. However, despite these favorable changes in the compositions of contact lens care solutions, none provide perfect in-eye performance without some measure of adverse effect on ocular tissues. Some degree of compromise to the tear film, tissue or cellular membrane integrity, such as corneal epithelial cell membrane integrity, remains with all current contact lens care solutions.
To date users have shown some preference for the polymeric biguanide quaternary ammonium based systems, which combine three steps of cleaning, disinfecting and rinsing in one. However, polymeric quaternary ammonium systems are usually weak in anti-fungal activities. Moreover, because of the positively charged nature of the polymeric biguanide and quaternary ammonium antimicrobial agents, they tend to be heavily adsorbed or bound to the contact lens materials (which are usually negatively charged), causing eye irritation. Therefore, there exists a need to improve contact lens care products to provide for simpler use with higher antimicrobial potency and less cornea irritation.
It is desirable to formulate a system having stronger anti-microbial properties than known systems, without increasing the adverse effects of contact lenses and contact lens care solutions on ocular tissues.
Previously it was thought that cetylpyridinium chloride (CPC), while useful as an anti-microbial agent for personal care product preservation, medical device disinfection and environmental decontamination, was unsuitable for use in soft contact lens cleaning solutions due to irritation to the eye caused by buildup in the contact lenses. Such irritation is believed to be caused by stimulation of the anterior ocular segment tissue, which may cause allergic reactions, inflammation, corneal erosion and the like. See, e.g., U.S. Pat. No. 4,908,147, to Tsao et al., which teaches that conventional quaternary germacides, such as benzalkonium chlorides, CPC and dodecyl triethanolamine hydrochloride tend to accumulate in hydrophilic soft contact lens materials. Similarly, Doi et al., in U.S. Pat. No. 5,994,405 note that bacteriocidal agents such as CPC are known to be readily adsorbed, particularly onto soft contact lenses. Once adsorbed, such bacteriocidal agents are hardly released, but accumulate on the lenses.
U.S. Pat. No. 3,954,644, to Krezanoski et al., teaches that cetylpyridinium chloride is a germicidal agent that is compatible with flexible silicone lenses, and is effective in concentrations ranging from about 0.001 to 0.03 percent of the overall solution. As is well known in the art, flexible silicone lenses are typically formed from silicone rubber, and are oxygen permeable, so they may be worn by the user for weeks on end. This may be contrasted with conventional soft contact lenses, which are hydrophilic lenses typically formed from a hydro-carbon polymer and which form hydrogels in equilibrium with water. Such soft contact lenses are typically water permeable, but not oxygen permeable, so it is typically recommended that the user remove their soft lenses at night. Flexible silicone lenses are also distinguished from silicone-hydrogel soft contact lenses, which also form hydrogels in equilibrium with water.
In the past, others have tried to incorporate CPC in ophthalmic solutions. For example Shinohara et al., in U.S. Pat. No. 5,998,488, teach the use of CPC as an antimicrobial preservative. However, Shinohara et al. also teach that a compound such as cyclodextrin must be included in the ophthalmic solution containing CPC at a concentration greater than 0.3% to inhibit the CPC from adsorbing to contact lenses. This is undesirable both from a manufacturing standpoint and from a complexity standpoint.
When used in association with soft contact lenses, high CPC concentration results in high CPC lens uptake, consequently causing high cornea irritation. While contact-lens-adsorption inhibitors may be used, the addition of contact-lens-adsorption inhibitors, such as cyclodextrin, also compromises CPC disinfecting efficacy. To compensate for the reduction of disinfecting efficacy due to the presence of the uptake inhibitors, the concentration of CPC concentration must be raised. This, in turn, results in an increase in CPC lens-uptake and cornea irritation.
In view of known limitations with contact lens care compositions, it would be advantageous to have contact lens care compositions, and methods of using the same, which are simpler to use, have higher antimicrobial potency, and show less corneal irritation.